1. Field of the Invention
The present invention relates to a novel method of administering propranolol, a .beta.-adrenergic-blocking agent, and to novel dosage forms containing propranolol adapted for nasal administration.
2. Description of the Prior Art
Propranolol, a .beta.-adrenergic-blocking agent, is widely used therapeutically, chiefly in the management of hypertension and in the treatment of angina pectoris, arrhythmias and other cardiac conditions, and migraine. The drug is, however, inefficiently and variably absorbed from oral dosage forms. Thus, Shand et al., Clin. Pharmacol. Therap. 11, 112-120 (1970), report a study in humans has shown that following oral administration of propranolol, peak plasma levels in five subjects given 80 mg oral doses varied seven fold, while levels for 10 mg intravenous doses in the same subjects varied only two fold. Furthermore, the bioavailability of propranolol in some subjects as calculated from the ratio of the area under the curve of an 80 mg oral dose and 10 mg I.V. dose was found to be as low as 16%. The variations in the blood levels as well as the low bioavailability for oral doses has been attributed by various researchers to the extensive metabolism of the drug in the gastrointestinal tract during the absorption process and/or to the effect of the first pass through the liver [Dollery et al., Ann, N.Y. Acad. Sci. 179, 109 (1971); Suzuki et al., Chem. Pharm. Bull. 20, 2731 (1972); and Garceau et al., J. Pharm. Sci. 67, 1360 (1978)].